Researchers analyzing venoms from spiders in the genus Loxosceles succeeded in identifying–as early as 1981–the toxin Sphingomyelinase D (SMaseD) as a sufficient cause of the dermonecrotic lesions that bites from these spiders sometimes produce in humans. The mode of action involves cleavage within the molecular structure of the eukaryotic membrane phospholipid sphingomyelin. Normal cleavages of phospholipids are necessary housekeeping processes for maintenance of healthy tissues, but when abnormal, wholesale cleavages occur in sphingomyelin, specifically between the choline and phosphate junction — i.e., at the D site — the result is actual tissue necrosis, or cell death.

The SMaseD toxin is somewhat unique, in that — in animals — it is presently known to be found only in Loxosceles spiders. A total of 100 species of spiders in the genus Loxosceles have been described, and all are either known or suspected of producing SMaseD in their venoms, though some (e.g., L. laeta, sometimes referred to as the Chilean recluse) appear to produce more than others. The group is known collectively as brown spiders (though many unrelated species are also brown), or recluse spiders, and is distributed worldwide. Many are native to the Americas, with approximately 13 species native to the United States.

Besides Loxosceles spiders, a few specific pathogenic bacteria are also known to produce SMaseD. These are Corynebacterium pseudotuberculosis (whose infections result in pathological conditions similar to Loxoscelism), C. ulcerans, Archanobacterium haemolyticum, and Vibrio damsela. This fact suggests that there may have been an evolutionary association between ancestors common to both the Loxosceles spiders and these bacteria. Molecular studies of the DNA sequences of both groups indicate, however, that any such association, if it exists at all, would have occurred in the far distant past, possibly as much as 150-250 million years ago. The genetic patterns displayed by the gene sequences present in modern specimens from both groups are too divergent to admit of a more recent association between them.

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